Aldeyra Therapeutics, Inc.

Hello, everyone, and welcome to the Aldira Therapeutics Phase 3 data call. My name is Carla, and I will be coordinating your call today. During the presentation, you will have the opportunity to ask questions by pressing star followed by 1 on your telephone keypad. If you change your mind, please press star followed by 2. I would now like to hand you over to Laura Nichols to begin. Laura, please go ahead when you're ready.

Thank you, and good morning, everyone. Yesterday, we issued a press release announcing achievement of the primary endpoint of a Phase III dry eye chamber trial of Aproxilab, an investigational new drug for the treatment of dry eye disease. A copy of the press release is available on the Investor in Media section of our website, www.aldera.com. The press release contains important information and should be read and considered in conjunction with the slides presented in prepared remarks made on today's call. With me today to discuss the top line results is Dr. Todd Brady, President and Chief Executive Officer of LDRRA. Turning to slide two. This presentation and various remarks which may be made during this presentation contain forward-looking statements regarding LDRRA, its investigational drug candidate, Roproxilab, and its plans, expectations, and opportunities, including regulatory and commercial activities. Forward-looking statements involve known and unknown risks, uncertainties, and other factors that may cause Eldera's actual results, performance, or achievements to be materially different from any future results, performance, or achievements expressed or implied by the forward-looking statements. These statements are based upon the information available to Eldera today and reflect Eldera's current views with respect to the future events and are based on assumptions and subject to risks and uncertainties, including the outcome and timing of the FDA's review, acceptance, and or approval of a potential NDA resubmission for Reproxilab and the adequacy of the data contained therein. Aldera assumes no obligation to update oral or written statements made today as circumstances change. Future events and actual results could differ materially from those projected in the company's forward-looking statements, including the results of operations and financial position. Additional information concerning factors that could cause results to differ materially from our forward-looking statements are described in greater detail in the press release issued this morning. and in our filings with the Security and Exchange Commission. I would now like to turn your attention to slide three and introduce Dr. Braden.

Thank you, Laura. We are thrilled to announce the positive results from our second phase three dry eye chamber trial to assess the activity of Reproxilab in reducing ocular discomfort associated with dry eye disease. Like the prior dry eye chamber trial relative to vehicle treatment, there was a highly statistically significant reduction in ocular discomfort following treatment with topical ocular reproxilab. And the results provide further support for a number of clinical trials highlighting the potential rapid clinical effect of reproxilab on reducing ocular discomfort. And we hope we'll enable NDA resubmission mid-year. To our knowledge, Reproxilab remains the first investigational drug with pivotal data supportive of acute and chronic activity in reducing symptoms of dry eye disease. As a way of background, following review of a new drug application or NDA of topical ocular Reproxilab for the treatment of dry eye disease, The FDA issued a complete response letter in November of 2023, which stated that at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye needed to be conducted. The letter did not identify any other review issues. Following FDA feedback under the special protocol assessment program and based on additional comments, We initiated a phase three dry eye chamber trial designed to satisfy the FDA's resubmission requirements. The trial achieved the primary endpoint, reproxilapse, statistically reduced ocular discomfort relative to vehicle. The NDA was resubmitted in October of last year. And last month, the FDA again issued a complete response letter which stated that at least one additional adequate and well-controlled study to demonstrate a positive effect on the treatment of ocular symptoms of dry eye needed to be conducted. In particular, the letter identified ocular discomfort baseline differences across treatment arms. Based in part on feedback received from the FDA after the CRL, we completed a second dry eye chamber trial designed to assess the effectiveness of Reproxilab in reducing ocular discomfort. The results announced yesterday were highly statistically significant in favor of Reproxilab over vehicle, and importantly, no notable differences in ocular discomfort baselines were observed between treatment groups. We also completed a field trial of Raproxilab, which while numerically in favor of Raproxilab and consistent with prior field trials, did not reach statistical significance. We believe that the recently completed dry eye chamber trial addresses the FDA feedback following review of the previously completed dry eye chamber trial resubmitted in the NDA last year. We have submitted the results of the dry eye chamber trial announced yesterday to the FDA and have requested a Type A meeting to discuss NDA resubmission. Pending the Type A meeting, we expect to resubmit the NDA mid-year consistent with prior guidance. The results of the phase three randomized double-masked vehicle-controlled dry eye chamber trial are presented on slide four. In the trial, which was substantially similar to that of the previously completed dry eye chamber trial, patients received randomized treatment before and during a dry eye chamber of 100 minutes in duration. The dry eye chamber, which is included in draft FDA guidance for drug development in dry eye disease, is a rigorously controlled low humidity environment designed to exacerbate dry eye disease signs and symptoms, which typically peak around 40 to 50 minutes after chamber entry. Unlike field trials, which typically require months of clinical testing and many clinic visits, the dry eye chamber allows for the elimination of variability in humidity, temperature, airborne particulate matter such as pollen, smoke, or pollution, and other factors known to influence dry eye disease. Most importantly, the chamber allows for the acute assessment of changes in signs and symptoms over a period measured in minutes. In this case, 100 minutes versus weeks or months in field trials. The primary endpoint was ocular discomfort score reported by the patients on a scale of zero or no discomfort to 100. the most severe discomfort during the dry eye chamber from 80 to 100 minutes after chamber entry. The FDA considers ocular discomfort a symptom of dry eye disease, and based on our conversations with the FDA regarding the Phase III dry eye chamber trials and analyses, also considers discomfort, dryness, and other commonly assessed symptoms to be substantially similar. Like the previously completed dry eye chamber trial, given that there were no sign requirements in the complete response letter for the NDA resubmission, and thus we believe that sign requirements have been met, ocular discomfort was the sole primary endpoint and there were no secondary or exploratory endpoints. The primary endpoint analysis was assessed using a mixed model for repeated measures across five time points, again, from 80 to 100 minutes after chamber entry. A period beginning 30 minutes after the second and final dose of Reproxilap or vehicle administered 50 minutes after chamber entry. 116 patients were enrolled. 58 received Reproxilap and 58 received vehicle. The primary endpoint of the phase three dry eye chamber trial was achieved with a p-value of 0.002. Although symptoms do not immediately exacerbate after chamber entry and instead exacerbate over time, Ocular's comfort score change from baseline was numerically lower with the Proxilab treatment than with vehicle treatment for all time points within the chamber and all time points during the primary assessment period from 80 to 100 minutes following chamber entry. The Ocular's comfort scores of patients treated with vehicle escalated consistently throughout the chamber In contrast, Ocular's comfort scores of patients treated with Reproxilab escalated at a lower rate after the first dose of drug, indicating prophylactic activity of Reproxilab, and at a substantially lower rate after the second dose of drug, indicating treatment activity of Reproxilab. During the primary endpoint assessment period, the peak change from baseline in the Reproxilab group was more than eight-fold lower than that of the vehicle group. There were no safety concerns identified and Reproxilab was observed to be well tolerated. No patients discontinued the clinical trial due to adverse events. And consistent with other clinical trials of Reproxilab, the most common adverse event was installation site irritation, which was exclusively mild and most commonly lasted less than one minute. To our knowledge, the results from this and the previously completed dry eye chamber trials represent the first positive phase three clinical trials in a dry eye chamber with a symptom as a primary endpoint. And therefore, we believe the results are uniquely supportive of the potential acute clinical effect of Raproxilab in reducing ocular discomfort and dry eye disease. In aggregate, the results are supportive of the rapid symptomological effect of Raproxilab in preventing exacerbation of ocular discomfort. in a setting designed to mimic the flares characteristic of dry eye disease. An issue highlighted in the prior dry eye chamber trial NDA review was an imbalance in ocular discomfort baseline scores across treatment arms, which prior to the treatment chamber was as much as seven points. As illustrated on slide five, No notable differences in baseline scores across treatment arms were observed before either the screening chamber or the treatment chamber. Using a Bayesian approach which models the probability of effectiveness, slide six summarizes the results of the recently completed field trial in conjunction with the two other field trials that we've conducted with the same dosing regimen. While the recently completed field trial did not reach statistical significance, the results numerically favored roproxilab, and in aggregate, the effect profile of roproxilab is statistically favored over that of vehicle. We expect to submit the field trial results to the planned NDA as supportive. Triad disease remains a pervasive and debilitating disease that is growing in prevalence and the clinical need remains for treatments that work quickly with sustained activity. Slide seven highlights the unique rapid activity of Reproxilab, which represents a novel mechanism of action that, based on the clinical data generated to date, potentially influences inflammation, vasomotor control, which could affect redness, and the sensation of discomfort on the ocular surface in patients with dry eye disease. Consistent with the prior dry eye disease chamber trial, yesterday's top line data suggests that in contrast to currently available therapies that require weeks or months for activity, Reproxilab has the potential to reduce ocular discomfort within minutes in a dry eye chamber. As such, Reproxilab continues to represent a potential paradigm shift in the way dry eye patients could be treated relative to standard of care. Slide eight summarizes the basis for NDA resubmission of Reproxilab for the treatment of dry eye disease. Specifically, at least one symptom trial was required by the FDA for resubmission, and the FDA provided feedback on the prior dry eye chamber trial as part of the most recent NDA review, and also the dry eye chamber trial announced yesterday, which achieved the primary endpoint without the baseline imbalance observed in the prior trial Thus, we expect to resubmit an NDA mid-year, consistent with prior guidance. The resubmission review period is expected to be six months. To our barest knowledge in patients with dry disease, Reproxilab is the first investigational drug with pivotal data supportive of acute and chronic activity in reducing symptoms, and the first investigational drug for chronic administration with pivotal data supportive of acute activity in reducing ocular redness. As previously disclosed, we expect that Reproxilab, if approved, could be the first dry eye disease drug for chronic administration with a label that highlights acute and chronic reduction in symptoms and acute reduction in ocular redness, a dry eye disease sign of particular importance to patients. Our clinical and regulatory milestones are summarized on slide nine. In addition to the expected resubmission of the NDA, we expect a variety of trial initiations and completions in a number of diseases characterized by inflammation and metabolic dysfunction, including those that affect the retina, skin, and central nervous system. For the remainder of 2025, we expect initiations of a Phase II clinical trial in atopic dermatitis and a Phase II-III clinical trial in retinitis pigmentosa. and IND submissions for dry age-related macular degeneration, metabolic inflammation. And over 2025 and 2026, we believe our catalyst news flow to be robust. Our pipeline is summarized on slide 10. In addition to dry eye disease, we believe that roproxilab, which is the subject of an option agreement with AbbVie, has completed clinical development for allergic conjunctivitis. pending further discussions with the FDA. If approved for dry eye disease, allergic conjunctivitis, which is one of the most common ocular diseases worldwide, could represent a supplemental NDA submission. If approved for both diseases, Reproxilab would represent the first drug for chronic administration that could be used to treat dry eye disease and allergic conjunctivitis, two persistently disturbing conditions that frequently occur together in the same patients. Importantly, we are well capitalized to execute on our pipeline based on prior guidance, current cash, cash equivalents, and marketable securities of over $100 million as of December 31st are expected to support operations into 2027, including clinical trial results in alcoholic hepatitis, atopic dermatitis, retinitis pigmentosa, dry age-related macular degeneration, Sjogren-Larsen syndrome, and metabolic inflammation. Consistent with prior guidance, our cash runway guidance does not include partnership or product revenue associated with Reproxilab. Operator, I would now like to open the call for questions.